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In the Pipeline: Skin-cancer drug tested in mice with model of Alzheimer's disease

A study released this February in the online version of the journal Science suggests that the drug bexarotene, which is approved by the U.S. Food and Drug Administration (FDA) for treating skin cancer, may also be beneficial in treating Alzheimer's disease (AD). Researchers at Case Western Reserve University in Cleveland, OH, found that bexarotene helped increase levels of apolipoprotein E (APOE) in mice whose brains had been genetically engineered to model aspects of AD damage. APOE helps carry cholesterol and other fats through the bloodstream.

That boost in APOE led to the clearing of a protein called amyloid beta and to improved behavior in the mice. One of the hallmarks of AD is the accumulation of amyloid beta between nerve cells (neurons) in the brain. In a healthy brain, amyloid beta is broken down and eliminated; in AD, it accumulates to form hard plaques.

“We were able to reverse all the cognitive problems in these mice with AD,” says principal investigator Gary E. Landreth, Ph.D., director of the Alzheimer Center at Case Western. “What this suggests is that, in mice, the AD process is fully reversible in the early stages of the disease. Bexarotene is the best drug anyone has ever seen in a mouse.”

News of the study spread fast. Neurologists and patient advocacy groups around the country were overwhelmed with calls from patients and caregivers asking to receive the drug. However, experts warn that just because a medication works in the lab doesn't mean it will be safe and effective in humans.

“We've seen other treatments that work in animal models of AD but don't work in people,” says Rachelle S. Doody, M.D., Ph.D., Fellow of the American Academy of Neurology and director of the Alzheimer's Disease and Memory Disorders Center at Baylor College of Medicine in Houston, TX.

“This was a mouse study, and mice are not a great model of the disease,” adds Dr. Landreth. The reason? Mice only live to be two years old and don't lose neurons, which is a hallmark of the disease in people.

Before bexarotene could became available to humans as an AD treatment, its safety and effectiveness would have to be proven in human trials. That process could take five to seven years and cost hundreds of millions of dollars, Dr. Landreth says.

“If the drug doesn't get into the human brain, we pack up and go home. If it doesn't affect signs of the disease, such as the amount of amyloid beta in the brain, then we also pack up and go home. If we fail, we want to go on to the next thing.”